{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:51:36Z","timestamp":1773391896264,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82161138027"],"award-info":[{"award-number":["82161138027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The absence of effective animal models for sporadic Alzheimer's disease (AD) remains a pivotal barrier to therapy development. Because methanol metabolism produces endogenous formaldehyde, a neurotoxic agent linked to cognitive decline, this study investigated whether chronic, low\u2010dose methanol exposure could recapitulate AD\u2010like pathology and cognitive deficits in rhesus monkey, thereby establishing a nonhuman primate animal model driven by this environmental\u2010metabolic insult.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult rhesus monkeys received low\u2010concentration methanol for 9\u2009months. Behavioral tests for cognition, locomotion, sleep, and vision were conducted. Postmortem analyses involved histopathological examination, immunohistochemistry, immunofluorescence, and Western blot to evaluate neuronal integrity, microglial activation, and the expression of key proteins associated with AD (amyloid\u2010\u03b2 [A\u03b2], phosphorylated tau, TAR DNA\u2010binding protein 43 [TDP\u201043]) and cellular stress (synaptic markers, mitochondrial fission, autophagy, and apoptosis\u2010related proteins).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chronic methanol exposure led to progressive cognitive and memory impairment without significant motor or visual deficits. Neuropathology revealed brain atrophy, neuronal loss, synaptic damage, microglial activation, and mitochondrial structural disorganization. Critically, the exposed animals exhibited hallmark AD\u2010like molecular alterations, including increased A\u03b2 deposition, tau hyperphosphorylation, and TDP\u201043 dysregulation. Furthermore, neurotoxicity was associated with elevated urinary formaldehyde, enhanced mitochondrial fission, increased autophagy, and elevated apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Chronic low\u2010dose methanol exposure in rhesus monkeys recapitulates progressive cognitive deficits and AD\u2010like neuropathological features. This model, driven by endogenous formaldehyde toxicity, effectively mimics key aspects of sporadic AD. Our findings shed light on the neurotoxic mechanisms of methanol and propose a reproducible and translationally relevant nonhuman primate model for studying AD pathogenesis and evaluating potential therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70142","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:58:55Z","timestamp":1772989135000},"page":"264-279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic methanol exposure induces cognitive impairment and Alzheimer's\u2010like pathology in rhesus monkeys"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7897-5188","authenticated-orcid":false,"given":"Hongwei","family":"Li","sequence":"first","affiliation":[{"name":"National Human Diseases Animal Model Resource Center, NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center 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